The goal of this proposal is to clarify the mechanisms whereby alveolar macrophages contribute to the defense of the lung and to lung injury. Many studies using peritoneal macrophages have led to our refined understanding on the molecular level of some of the individual events which comprise the defense function of this cell. On the other hand, the function of alveolar macrophages in the immunological resistance and pathology of the lung is not nearly as well understood. We plan to investigate the role of certain macrophage directed lymphocyte mediators, migration inhibitory factor (MIF) and macrophage activating factor (MAF), in the defense functions of the alveolar macrophage. These substances are elaborated by antigen sensitized and stimulated lymphocytes in the course of cellular immune reactions and increase the defense capacities of these cells. The role of certain neutral proteinases associated with the alveolar macrophage which are involved in the pathology of lung disease will also be investigated. Finally, we intend to determine the role of collagen in the immunity and inflammation of fibrotic lung diseases.